Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
- Conditions
- Catecholaminergic Polymorphic Ventricular Tachycardia
- Interventions
- Registration Number
- NCT01117454
- Lead Sponsor
- Vanderbilt University Medical Center
- Brief Summary
The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce ventricular ectopy on exercise test compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia.
- Detailed Description
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a genetic arrhythmia syndrome characterized by frequent ventricular ectopy and polymorphic, classically bidirectional ventricular tachycardia with physical or emotional stress, which also carries a risk of ventricular fibrillation and sudden death, despite no structural heart abnormality. Treatment consists of beta-blockers and/or calcium channel blockers, but up to 30% of patients require implantable cardioverter-defibrillators (ICDs) due to recurrent symptoms on medical therapy. In an animal model, flecainide was found to directly target the molecular defect in CPVT. In a retrospective clinical study in patients with CPVT we have seen improvement of ventricular ectopy on exercise tests when flecainide is added to standard therapy. We propose a prospective trial of flecainide added to standard therapy in CPVT patients to test the hypothesis that flecainide will reduce ventricular ectopy on exercise testing compared to placebo plus standard therapy.
This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (flecainide or placebo) for at least 3 months and, after a 1 week wash-out, treatment B (placebo or flecainide) for at least 3 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
-
Clinical diagnosis of CPVT, based on:
A. reproducible polymorphic or bidirectional ventricular tachycardia with exercise OR B. Ventricular ectopy on exercise test with RYR2 or CASQ2 mutation
-
Functioning ICD in place
-
On stable dose of standard therapy defined as the maximal tolerated dose of beta-blocker and may include a calcium channel blocker
Patients on flecainide or mexiletine are also eligible for enrollment after a 1 week "washout" period during which flecainide or mexiletine is discontinued, and standard therapy alone is used.
- Females who are pregnant or plan to be pregnant during the study period
- Children < 5 years of age
- Patients unable to perform treadmill exercise
- Patients with significant structural heart disease
- Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation
- Patients with known hypersensitivity to flecainide
- Patients on amiodarone
- Patients not expected to comply with follow-up
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Flecainide then placebo Beta blocker In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers. Flecainide then placebo Placebo In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers. Placebo then flecainide Placebo In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers. Placebo then flecainide Beta blocker In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers. Flecainide then placebo Flecainide Acetate In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers. Placebo then flecainide Flecainide Acetate In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers.
- Primary Outcome Measures
Name Time Method Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing 3 months Hypothesis: the addition of oral flecainide to standard therapy will reduce ventricular ectopy and/or VT on treadmill exercise treadmill testing in patients with CPVT, compared to placebo plus standard therapy.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (10)
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Cook Children's Hospital
🇺🇸Fort Worth, Texas, United States